Conventional non-steroid type anti-inflammatory drug (NSAID) causes digestive tract disorder such as gastric ulcer, etc. from its function and mechanism, so that they have a problem in continuous use for a long period of time. Also, a disease modified type anti-rheumatoid drug (DMARD) which is used for chronic rheumatism as the etiotropic purpose has not yet been shown its clear medical effect stably as of today. On the other hand, an antibody theraphy of TNF-α which is a kind of inflammatory cytokines and considered to induce various events after occurrence of inflammation shows remarkable effects on chronic rheumatism, and exemplifies that inhibition of production of cytokines is preferred as a mechanism for an anti-rheumatoid drug, etc. Moreover, with regard to cytokines such as IL-1, IL-6, IL-8, etc., various functions as inflammatory mediators have been clarified. p38MAP kinase which has been cloned as a homolog of MAP kinase pertains to inhibition of production of these inflammatory cytokines and to a signal transduction pathway coupled with a receptor, and thus, a novel inflammatory cytokine-inhibiting agent due to p38MAP kinase inhibition is now expected to be a treating agent as an antipyretic, analgesic and anti-inflammatory agent with a different function and mechanism from the conventional ones, and for diseases including autoimmune disease such as chronic rheumatism, bone diseases such as osteoporosis, and other diseases to which these cytokines pertain.
There are conventional pyrazole compounds having a function of inhibiting production of these inflammatory cytokines (for example, WO 98/52940A publication, WO 00/31063A publication, WO 95/31451A publication, WO 02/57265A publication and WO 00/39116A publication), but it has been desired to develop a compound having more excellent in medical effects, pharmacokinetic profile and safety.
An object of the present invention is to provide a series of the pyrazole compounds or pharmaceutically acceptable salts thereof showing more potent medical effect, excellent pharmacokinetic profile and high safety in the research of low molecular compounds having a function of inhibiting production of inflammatory cytokines due to the above-mentioned p38MAP kinase inhibition.